Expert interview:Gene-Expression Signatures -Clinical Implications for Breast Cancer

[heblaj01]

http://www.radiology.medscape.com/viewarticle/551097_print
Gene-Expression Signatures -- Clinical Implications for Breast Cancer Therapy: An Expert Interview With Dr. Joseph Sparano Posted 01/25/2007

One startling statement in this interview is:
"A prime example would be the ability to "fine-tune" treatment for patients with ER-positive, lymph-node negative breast cancer -- which accounts for about 125,000 cases diagnosed in the United States each year. About 90,000 of those patients would be potentially suitable candidates for adjuvant chemotherapy. However, we know that about 80% to 85% of those patients can be cured with endocrine therapy, and that adding chemotherapy reduces the risk of recurrence by only, on average, 1% to 5%. So we are clearly overtreating the vast majority of patients. The challenge, therefore, will be to develop markers that can identify which patients with low-risk, ER-positive disease truly do need treatment".

[AlaskaAngel]

Well, I'm encouraged by the words too, Heblaj01, but am not as sure about use of the word "cure" considering the problem of eventual endocrine resistance. Maybe I just don't quite understand everything in the articles about us ER+ node-negatives, or about eventual endocrine resistance?

Respectfully,

A.A.

[heblaj01]

What surprised me even more than the word "cure" is the awfull number of patients who have to unecessarily endure chemo because there is no markers to determine if they are in the small minority which really needs chemo in addition to endocrine treatment.

[Jean]

Heblajo1,
How about the Oncotype DX test for those women who are er positive and
node neg. to determine recurrence risk? I believe this is being used to
help those women who are on the fence with chemo.

Please advise....many thanks,

Kind Regards,
Jean

[heblaj01]

Jean,
The answer to your question is that the OncotypeDX test is giving fairly valid indications only for low & high Recurrence Scores leaving 40 to 60% of patients with intermediate scores in limbo as to whether or not they need chemo in addition to hormonal treatment:
"Dr. Sparano: We have demonstrated that for some patients -- for example, those with very low or very high Recurrence Scores with OncotypeDX -- we can be fairly confident making recommendations regarding treatment. For those who have a low Recurrence Score, for instance, we can recommend hormonal therapy alone with great confidence because we know those patients have a very low risk of relapse with hormonal therapy alone and will be unlikely to benefit from chemotherapy. We also know that for patients who have a very high Recurrence Score, adding chemotherapy is associated with a substantial reduction in the risk of relapse. However, in patients who have a mid-range score, which can account for anywhere from 40% to 60% of all patients tested, the score is not necessarily informative because we do not know for sure whether chemotherapy will be useful in reducing the risk of recurrence in that group. This is the question that the TAILORx [Trial Assigning Individualized Options for Treatment] trial is designed to define.

Other issues include whether we can use these assays to make treatment decisions in patients with lymph-node-positive breast cancer, and in HER-2-positive or ER-negative breast cancer, and that work is now ongoing".

More research will be needed to find pronostic markers which will help almost all categories of patients in selecting their optimal treatment.

[AlaskaAngel]

That pretty much leaves most HER2's in no-person's-land, because the TAILOR-X trial specifically excludes HER2 positives. There is also a conspicious lack of any discussion about the use of Oncotype Dx for those HR+ HER2 positives who did go through chemo to provide any direction for further treatment. And much of the comments I've seen here about the use of Oncotype Dx prior to treatment indicate that anyone who is considered really HER2 positive is pretty much automatically recommended to have chemo. So TAILOR-X and Oncotype Dx don't do much for us, although hopefully they will help some who aren't HER2 positive.

AlaskaAngel

[heblaj01]

AlaskaAngel

There may be more info on the oncotype/dx test in the audio interviews of the latest BREAST CANCER UPDATE 2006 issue 7 (actually issue 8, my mistake) I posted a few weeks ago. More than one of the oncs commented on it.

[gdpawel]

The genetic analysis of Oncotype DX predicts which women will have a greater chance of breast cancer recurrence. The test looks at 21 genes that influence the behavior of breast cancer cells. Until this test, it had been difficult to pinpoint which women would benefit most from chemotherapy, and those which wouldn’t.

MammaPrint is another genetic test that could help patients with early-stage breast cancer predict their chance of relapse, information that could save many patients from unnecessary chemotherapy. This test looks at the expression of 70 genes linked to breast cancer with an accuracy level of 96.7% as determined by a study published in the New England Journal of Medicine.

Another molecular-targeted breast prognostic test called Mammostrat, is validated with the usual, retrospective, non-randomized study using archival tissues and uniform batch processing and slide interpretation. It utilizes five immunohistochemical (IHC) biomarkers to classify patients into high, moderate, or low-risk categories for disease recurrence.

These new gene expression profiling tests enable the oncologist and breast cancer surgeon to more accurately determine who should be treated and who should not be treated with chemotherapy, but they cannot predict chemo response.

These laboratory tests are a tool for the oncologist. The oncologist should take advantage of all the tools available to him/her to treat a patient. And since studies show that only 25-30% of patients do respond to chemotherapy that is available to them (and even less for "targeted" drugs), there should be due consideration to looking at the advantage of molecular and cellular assay tests to the resistance that has been found to chemotherapy drugs.

These tests can enhance the ability to distinguish between "low" risk and "high" risk patients. Patients in the high-risk group, who would benefit from chemotherapy can then be pre-tested with a "functional" bio-marker to see what treatments have the best opportunity of being successful, and offers a better chance of tumor response resulting in progression-free survival, while those in the lower-risk groups can be spared the unnecessary toxicity, particularly associated with ineffective treatment.

Every breast cancer patient should have her own unique chemotherapy trial based on consultation of pathogenic profiles and drug sensitivity testing data. Research and application of these tests are being encouraged by growing patient demands, scientific advances and medical ethics. These tests are not a luxury but an absolute necessity, and a powerful strategy that cannot be overlooked.

http://cancerfocus.org/forum/showthread.php?t=734